The Scope of Pre- and Probiotics as an Add-on to Proton-pump Inhibitors in Various Clinical Indications.

OBJECTIVE: To understand the national pattern of proton-pump inhibitor (PPI) prescriptions and to disseminate evidence-based recommendations for using probiotics as an adjunct to PPIs across diverse clinical indications. METHODS: Healthcare professionals' (HCPs) inputs and views were collected through a survey (n = 1,007) and four round table meetings (RTMs, n = 4). A standardized questionnaire focusing on the utilization of PPIs in clinical practice was developed, deliberated upon, and assessed by experts specializing in the treatment of diverse acid-related gastrointestinal (GI) conditions across various geographical regions. RESULTS: Of the total 1,007 contributors, most (43.40%) opined that 10-30% of their patients were prescribed PPI for a long duration. The majority of contributors commonly prescribed PPIs for the prophylaxis of gastroesophageal reflux disease (GERD)-induced gastritis (70.90%), peptic ulcer disease (58.39%), and various GI conditions. The majority of contributors (91%) agreed or strongly agreed that long-term use of PPIs disturbs the GI flora. Antibiotic-associated diarrhea (AAD) (78.05%) was the most preferred indication for using pre- and probiotics. The duration for co-prescription varied, with a substantial portion advocating for 1-4 weeks (49.65%), while others supported durations of 4-8 weeks or beyond. Around 85% of contributors/HCPs agreed or strongly agreed on prescribing pre- and probiotics as prophylaxis to prevent GI disturbances. The study emphasized the growing trend of patient-centered co-prescription of PPIs and pre-/probiotics, with a majority of contributors favoring this approach. CONCLUSION: The results underscore the importance of informed prescribing practices, including the co-prescription of probiotics, to mitigate potential side effects associated with long-term PPI use and optimize patient well-being.

Hepatocrinology.

Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.

Localization value of ictal turning prone.

PURPOSE: Ictal semiology complements ictal EEG in identifying the likely epileptogenic zone. Ictal turning prone (ITP) with body turning of 90 ° or more can be seen with frontal lobe epilepsies. The aim of our study was to evaluate the localizing value of ITP in a general population of patients undergoing long term video-EEG monitoring. METHODS: We reviewed our epilepsy monitoring unit database for adult patients with recorded habitual seizures with ITP. All 16 patients identified had continuous video-EEG monitoring using standard scalp electrodes; eight patients also had intracranial EEG monitoring. We only included focal seizures without evolution to bilateral tonic-clonic activity. RESULTS: We identified 16 patients with ITP, mean age of 32.5 years (range 18-50). ITP was consistently seen in at least one focal impaired awareness seizure of all patients. Ictal onset zone on scalp EEG was left temporal in five, right temporal in three, left frontal convexity in two, right frontal convexity in two, probable right medial frontal in three and probable left medial frontal in one patient. Direction of ITP was uni-directional in 12 patients while 4 patients had ITP in opposite direction in different seizures. Nine patients underwent epilepsy surgery; five patients had Engel class I outcome and four patients had Engel class III outcome. CONCLUSIONS: Ictal turning prone does not have a consistent single localizing or lateralizing value and can be seen with various epileptogenic zones including medial frontal, lateral frontal or temporal. ITP direction can vary even with a single epileptogenic zone.

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India.

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm3, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.

Deep Brain Stimulation Battery Longevity: Comparison of Monopolar Versus Bipolar Stimulation Modes.

BACKGROUND: Deep brain stimulation is an effective treatment for movement disorders, but it is relatively complex, invasive, and costly. Little is known about whether stimulation mode alters pulse generator (battery) longevity in routine clinical care. OBJECTIVE: To compare battery longevity during monopolar versus bipolar stimulation in patients who underwent deep brain stimulation for movement disorders. METHODS: We evaluated 2,902 programming adjustments and calculated the average stimulator settings for 393 batteries in 200 unique patients with Parkinson's disease and essential tremor. We classified the pulse generators into different stimulation modes (monopolar, bipolar, tripolar, double monopolar) and compared battery longevity with Kaplan Meier survival analyses using the log rank test. We exclusively implanted the Medtronic 3387 lead with adjacent electrode contacts separated by 1.5 mm. RESULTS: The mean pulse generator longevity was 47.6±1.6 months regardless of diagnosis or stimulation mode. Bipolar stimulation mode was associated with greater longevity than monopolar stimulation (56.1±3.4 versus 44.2±2.1 months, p=0.006). This effect was most pronounced when stimulation parameters were at low to moderate intensity settings. Double monopolar configuration was associated with less pulse generator longevity than conventional stimulation modes (37.8±5.6 versus 49.7±1.9, p=0.014). CONCLUSION: IPGs initially programmed in bipolar mode provided one year of additional battery longevity versus monopolar mode in this large retrospective series of patients with essential tremor and Parkinson's disease. Given satisfactory efficacy for motor symptoms, bipolar stimulation mode is a feasible alternative programming strategy at the initiation of DBS therapy.

Personalities of patients with nonepileptic psychogenic status.

The purposes of this study were to determine whether personalities of patients with nonepileptic psychogenic status (NEPS) are different from those of patients with typical intermittent psychogenic nonepileptic seizures (iPNES) using the Personality Assessment Inventory (PAI) and to compare their PAI profiles with the population norms. We hypothesized that patients with NEPS have more psychopathology compared with patients with iPNES and that, as a group, patients with PNES (iPNES+NEPS) would have more psychopathology compared with healthy individuals. We first compared the PAI profiles of patients with iPNES and NEPS and then the profiles of patients with NEPS, iPNES, and PNES with population norms in order to assess which PAI specific scales differed between groups in order to better characterize the psychopathology of PNES. All patients admitted for diagnostic evaluation to the epilepsy monitoring unit (EMU) were prospectively approached for participation. All patient/family interviews were conducted by an epileptologist, and the diagnosis of iPNES or NEPS was confirmed in all cases through video/EEG and/or family interview. The population norms for PAI were obtained from the manual. Of the 224 approached patients, 130 completed the PAI, and included 43 iPNES and 11 with NEPS. There were no significant differences between the two groups in regard to demographic or PAI profiles. Comparison with population norms revealed the presence of abnormal personality profiles on all scales in patients with iPNES, NEPS, or PNES. We conclude that while the occurrence of NEPS is relatively common in patients with PNES, the demographic characteristics and personality profiles of patients with NEPS are not different from those of patients with iPNES. We also confirmed the presence of significant psychopathology in the group with PNES when compared with population norms.

Patient Selection for Drip and Ship Thrombolysis in Acute Ischemic Stroke.

OBJECTIVES: The drip and ship model is a method used to deliver thrombolysis to acute stroke patients in facilities lacking onsite neurology coverage. We sought to determine whether our drip and ship population differs from patients treated directly at our stroke center (direct presenters). METHODS: We retrospectively reviewed consecutive patients who received thrombolysis at an outside facility with subsequent transfer to our center between 2009 and 2011. Patients received thrombolysis after telephone consultation with a stroke specialist. We examined demographics, vascular risk factors, laboratory values, and stroke severity in drip and ship patients compared with direct presenters. RESULTS: Ninety-six patients were identified who received thrombolysis by drip and ship compared with 212 direct presenters. The two groups did not differ with respect to sex, ethnicity, vascular risk factors, or admission glucose. The odds ratio (OR) of arriving at our hospital as a drip and ship for someone 80 years or older was 0.31 (95% confidence interval [CI] 0.15-0.61, P < 0.001). Only 21% of drip and ship patients were black versus 38% of direct presenters (OR 0.434, 95% CI 0.25-0.76, P = 0.004). Even after stratifying by age (<80 vs ≥80), a smaller proportion of drip and ship patients were black (OR 0.44, 95% CI 0.24-0.81, P = 0.008). Furthermore, we found that fewer black patients with severe strokes arrived by drip and ship (OR 0.33, 95% CI 0.11-0.98, P = 0.0028). CONCLUSIONS: Our study showed that a smaller proportion of blacks and older adults arrived at our center by the drip and ship model. This may reflect differences in how patients are selected for thrombolysis and transfer to a higher level of care.

Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt.

BACKGROUND: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples.

Safety of intravenous tissue plasminogen activator administration with computed tomography evidence of prior infarction.

BACKGROUND: Prior stroke within 3 months excludes patients from thrombolysis; however, patients may have computed tomography (CT) evidence of prior infarct, often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pretreatment CT is a predictor of hemorrhagic complications and functional outcomes after the administration of intravenous (IV) tissue plasminogen activator (tPA). METHODS: We retrospectively analyzed consecutive patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs were reviewed for evidence of any prior infarct. Further review determined if any hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH) were present on repeat CT or magnetic resonance imaging. Outcomes included sICH, any HT, poor functional outcome (modified Rankin Scale score of 4-6), and discharge disposition. RESULTS: Of 212 IV tPA-treated patients, 84 (40%) had evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023). Patients with prior infarcts on CT did not experience more sICH (4% versus 2%; P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and were less often discharged to home or inpatient rehabilitation center (61% versus 73%; P=.065). CONCLUSIONS: Visualization of prior infarcts on pretreatment CT did not predict an increased risk of sICH in our study and should not be viewed as a reason to withhold systemic tPA treatment after clinically evident strokes within 3 months were excluded.

Shorter pulse generator longevity and more frequent stimulator adjustments with pallidal DBS for dystonia versus other movement disorders.

BACKGROUND: Deep brain stimulation has become a routine therapy for movement disorders, but it is relatively invasive and costly. Although stimulation intensity relates to battery longevity, less is known about how diagnosis and stimulation target contribute to this clinical outcome. Here we evaluate battery longevity in movement disorders patients who were treated at a tertiary referral center. OBJECTIVE: To compare single channel pulse generator longevity in patients with movement disorders. METHODS: With Institutional Review Board approval, we evaluated 470 consecutive Soletra implants for routine care. Battery longevity was estimated with Kaplan-Meier analyses, and group comparisons were performed with the log rank mean test. The frequency of clinic encounters for ongoing care was evaluated across diagnoses with analysis of variance (ANOVA). RESULTS: The mean pulse generator longevity was 44.9 ± 1.4 months. Pallidal DBS for dystonia was associated with shorter battery longevity than subthalamic and thalamic DBS for Parkinson's disease and essential tremor (28.1 ± 2.1 versus 47.1 ± 1.8 and 47.8 ± 2.6 months, respectively, mean ± standard error, P < 0.001), and dystonia patients required more frequent clinic visits for routine care (F = 6.0, P = 0.003). Pallidal DBS for Parkinson's disease and thalamic DBS for cerebellar outflow tremor were associated with shorter battery longevity, as well (35.3 ± 4.6 and 26.4 ± 4.3 months, respectively). CONCLUSIONS: Pallidal DBS for dystonia was associated with shorter battery longevity and more frequent stimulator adjustments versus DBS for Parkinson's disease and essential tremor. Characteristics of the stimulation target and disease pathophysiology both likely contribute to battery longevity in patients with movement disorders.

Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an inflammatory process associated with poor outcomes in acute ischemic stroke (AIS) patients. However, no study to date has investigated predictors of SIRS in AIS patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS: Consecutive patients were retrospectively reviewed for evidence of SIRS during their acute hospitalization. SIRS was defined as the presence of 2 or more of the following: (1) body temperature less than 36°C or greater than 38°C, (2) heart rate greater than 90, (3) respiratory rate greater than 20, or (4) white blood cell count less than 4000/mm or greater than 12,000/mm or more than 10% bands for more than 24 hours. Those diagnosed with an infection were excluded. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cutoff of ≥65% or area under the curve of .6 or more. RESULTS: Of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be black (61% versus 54%; P = .011), have lower median total cholesterol at baseline (143 versus 167 mg/dL; P = .0207), and have history of previous stroke (51% versus 35%; P = .0810). Ranging from 0 to 6, the SIRS prediction score consists of African American (2 points), history of hypertension (1 point), history of previous stroke (1 point), and admission total cholesterol less than 200 (2 points). Patients with an SIRS score of 4 or more were 3 times as likely to develop SIRS when compared with patients with a score of ≤3 (odds ratio = 2.815, 95% confidence interval 1.43-5.56, P = .0029). CONCLUSIONS: In our sample of IV tPA-treated AIS patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA.

Safety of protocol violations in acute stroke tPA administration.

BACKGROUND: Intravenous (IV) tissue plasminogen activator remains the only approved therapy for acute ischemic stroke (AIS) in the United States; however, less than 10% of patients receive treatment. This is partially because of the large number of contraindications, narrow treatment window, and physician reluctance to deviate from these criteria. METHODS: We retrospectively analyzed consecutive patients who received IV thrombolysis at our stroke center for National Institute of Neurological Disorders and Stroke (NINDS) protocol violations and rates of symptomatic intracerebral hemorrhage (sICH). Other outcome variables included systemic hemorrhage, modified Rankin Scale at discharge, and discharge disposition. RESULTS: A total of 212 patients were identified in our stroke registry between 2009 and 2011 and included in the analysis. Protocol violations occurred in 76 patients (36%). The most common violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure management (15%), elevated prothrombin time (PT) or partial thromboplastin time (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%), and stroke within 3 months (3%). There were no significant differences in any of the safety outcomes or discharge disposition between patients with or without protocol violations. Controlling for age, National Institutes of Health Stroke Scale on admission, and glucose on admission, there was no significant increase in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who had protocol violations. CONCLUSIONS: Despite more than one third of patients receiving thrombolysis with protocol violations, overall rates of hemorrhage remained low and did not differ from those who did not have violations. Our data support the need to expand access to thrombolysis in AIS patients.

Systemic inflammatory response syndrome in tissue-type plasminogen activator-treated patients is associated with worse short-term functional outcome.

BACKGROUND AND PURPOSE: Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator-treated patients. METHODS: Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature<36°C or >38°C, heart rate>90, respiratory rate>20, and white blood cells<4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded. RESULTS: Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre-tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16-5.73; P=0.0197). CONCLUSIONS: In our sample of tissue-type plasminogen activator-treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay.

The Potential Impact of Maintaining a 3-Hour IV Thrombolysis Window: How Many More Patients can we Safely Treat?

BACKGROUND: In 2008, the European Cooperative Acute Stroke Study-3 (ECASS-3) demonstrated that intravenous-tissue plasminogen activator could be safely administered for acute stroke patients presenting between 3 and 4.5 hours from symptom onset. Recently, the Food and Drug Administration rejected expansion of this time window in the United States. We sought to determine how many fewer patients would be treated by maintaining this restricted time window. METHODS: We reviewed charts from patients who received intravenous thrombolysis at the University of Alabama at Birmingham between January 2009 and December 2011. Patients were divided into two groups (treated within 3 hours of onset, treated between 3 and 4.5 hours from onset). Demographics, stroke severity and protocol deviations according to the ECASS-3 trial were collected. Our safety measures were any hemorrhagic transformation, symptomatic intracerebral hemorrhage and systemic hemorrhage. RESULTS: Two hundred and twelve patients were identified, of whom 192 were included in our analysis. A total of 36 patients (19%) were treated between 3 and 4.5 hours. No statistical differences were seen between age (p=0.633), gender (p=0.677), race (p=0.207) or admission stroke severity (p=0.737). Protocol deviations from the ECASS-3 criteria were found in 20 patients (56%). These were primarily age > 80 and aggressive blood pressure management. Despite these deviations, we did not see significant increases in the rates of adverse events in patients treated in the extended time window. CONCLUSIONS: Our data are consistent with previously reported international data that IV thrombolysis can safely be used up to 4.5 hours from symptom onset. Restricting the time window to 3 hours would have resulted in almost one-fifth fewer patients treated at our center.

Hemorrhagic Transformation (HT) and Symptomatic Intracerebral Hemorrhage (sICH) Risk Prediction Models for Postthrombolytic Hemorrhage in the Stroke Belt.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) remains the most feared complication of intravenous tissue plasminogen activator (IV tPA) treatment. We aimed to investigate how previously validated scoring methodologies would perform in treated patients in two US Stroke Belt states. METHODS AND RESULTS: We retrospectively reviewed consecutive patients from two centers in two Stroke Belt states who received IV tPA (2008-2011). We assessed the ability of three models to predict sICH. sICH was defined as a type 2 parenchymal hemorrhage with deterioration in National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or death. Among 457 IV tPA-treated patients, 19 (4.2%) had sICH (mean age 68, 26.3% Black, 63.2% female). The Cucchiara model was most predictive of sICH in the entire cohort (AUC: 0.6528) and most predictive of sICH among Blacks (OR = 6.03, 95% CI 1.07-34.1, P = 0.0422) when patients were dichotomized by score. CONCLUSIONS: In our small sample from the racially heterogeneous US Stroke Belt, the Cucchiara model outperformed the other models at predicting sICH. While predictive models should not be used to justify nontreatment with thrombolytics, those interested in understanding contributors to sICH may choose to use the Cucchiara model until a Stroke Belt model is developed for this region.

Clinical presentation of celiac disease among pediatric compared to adolescent and adult patients.

BACKGROUND: Celiac disease (CD) is being increasingly recognized in adults though a majority of patients continue to be diagnosed in childhood. AIM: To compare the clinical presentation and profile of newly diagnosed pediatric and adolescent/adult CD patients. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with CD between year 1997 and 2007 in the pediatric group, and between year 2000 and 2007 in the adolescent/adult group was done for clinical presentation, endoscopic findings and duodenal histology. RESULTS: A total of 434 children and 298 adults were studied. The mean age of diagnosis was 6.5 ± 2.5 years (1-11 years) in children and 29.3 ± 13.3 years (6-73 years) in adolescent/adults. The mean duration of symptoms before diagnosis was 3.5 ± 2.5 years in children and 4.9 ± 4.6 years in the latter. Diarrhea as the presenting symptom was seen in 74 % of children and 58.7 % of adolescent/adults. Anemia (on investigations) was seen in 84 % of children and 94 % of adolescent/adults. CONCLUSIONS: Pediatric patients of CD present more often with typical features than adults. Atypical presentations are more common in adults and the latent period for diagnosis is also longer in adolescent/adults. There is a need for increasing awareness about CD, both among pediatricians and physicians caring for adult patients.

Predictors of outcome in acute-on-chronic liver failure in children.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is associated with a high mortality rate in the absence of liver transplantation. There is limited data on predictors of survival in ACLF in children. Therefore, we prospectively studied the predictors of outcome of ACLF in children. METHODS: A prospective evaluation of 31 children in the age group of 1-16 years who fulfilled the criteria for ACLF according to Asian Pacific Association for the Study of the Liver (APASL) 2008 consensus was done. All consecutive children were evaluated for etiology, diagnosis and severity of ACLF. For grading of organ dysfunction, the sequential organ failure assessment (SOFA) score was calculated. SOFA constitutes the parameters of respiration, coagulation, cardiovascular system, central nervous system, and renal and liver functions. We evaluated possible correlation between outcomes and different variables. RESULTS: Of the 31 children who fulfilled the criteria for ACLF, the common underlying chronic liver diseases (CLD) were autoimmune hepatitis (AIH) in 41.9% and Wilson disease in 41.9% of the patients. Superinfection with hepatitis A virus (HAV) (41.9%) was the most common etiology of acute deterioration. To find the best predictor for outcome, linear regression analysis was performed. Multivariate analysis revealed that the SOFA score and the International Normalized Ratio (INR) were predictors of survival. Six (19.4%) patients died. Causes of death were multiorgan failure in four and liver failure in two patients. CONCLUSION: The mortality in ACLF is 19.4% and the causes of death were multiorgan failure and liver failure. The SOFA score and INR were predictors of outcome of ACLF in children.

Transcription factor PITX3 gene in Parkinson's disease.

PITX3 is a transcription factor important for the differentiation and survival of midbrain dopaminergic neurons during the development. Recent reports suggest that single nucleotide polymorphisms (SNP) in the gene may be associated with Parkinson's disease (PD). To verify their findings and to determine the nature of the association in a subset of our PD patients we have analyzed two PITX3 SNPs (rs2281983 and rs4919621) in 265 PD patients and compared them with 210 age-matched healthy controls. Our data show that the substitutions of C/T in SNP1 and A/T in SNP2 are significantly higher in PD, and this finding is even more robust in young onset and familial PD as compared with age-matched healthy controls. Our findings indicate that PITX3 may play a role in the pathogenesis of PD.

Familial prevalence of celiac disease.

BACKGROUND AND OBJECTIVE: Serological screening enables us to detect patients of celiac disease (CD) before they develop serious complications. This study was planned to assess the prevalence of CD in the family members of index cases by serological screening. PATIENTS AND METHODS: A prospective study was conducted on 50 children diagnosed to be having CD. Serological screening of the family members of index cases was done and those showing positivity for the screening tests were further subjected to endoscopic duodenal biopsy for histopathological examination. RESULTS: A total of 164 members of 50 celiac families were initially screened for antibodies. Antibody picked up 32.9% by IgG anti-gliadin (AGA), 20.7% by endomysial antibody, 19.5% by tissue transglutaminase and 14.6% IgA AGA as seropositive for CD. Endoscopic findings characteristics for CD were present in only eight family members. CONCLUSION: Family members of CD cases represent potential cases of CD.

Zinc supplementation to patients with celiac disease--is it required?

BACKGROUND AND OBJECTIVES: This study was conducted to evaluate plasma levels of zinc in children with celiac disease, to correlate plasma zinc levels among the celiacs with short stature and diarrhea and to compare plasma zinc levels in deficient patients on gluten-free diet (GFD) with or without 4 weeks of zinc supplementation. METHODS: A total of 134 patients underwent plasma zinc estimation at baseline and after a four week period. Zinc-deficient patients were randomly assigned to two groups. Group G (n = 48) received GFD without zinc supplementation, Group G + Z (n = 48) received GFD with zinc supplementation for 4 weeks. RESULTS: The rise in plasma Zinc levels was significant in each group regardless of zinc supplementation but similar when compared in the two groups after 4 weeks. Mean zinc levels at baseline and increase in zinc levels were statistically similar at 4 weeks in patients with diarrhea and short stature. CONCLUSIONS: Zinc levels rise with GFD irrespective of zinc supplementation.